Intrathecal Injection Pemetrexed And Bevacizumab in Patients With Leptomeningeal Metastases in NSCLC

Inclusion Criteria:

* Age ≥ 18 years;
* ECOG PS score 0-3. ECOG PS score 2 or 3 should be due to leptomeningeal metastases.
* Patients with pathologically diagnosed non-small cell lung cancer with cerebrospinal fluid and/or MRI diagnosis of leptomeningeal metastasis(LM);
* Unsatisfactory efficacy of LM,which defined as disease progression in LM,or LM-related neurological progression, while patients received standard systemic anti-tumor treatment;
* Expected survival time ≥ 1 month;
* The laboratory test results meet the following criteria:Hemoglobin ≥ 90 g/L, neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L; Total bilirubin ≤ 1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN ; Creatinine≤ 2.0 × ULN,or Creatinine clearance rate (CrCl) ≥ 50 mL/min;
* Females of child-bearing potential agree to use contraception during the study period and for 6 months after the completion of the study; patients who have had a negative serum or urine pregnancy test within seven days prior to enrollment in the study and who are not breastfeeding; and males agreeing to use contraception during the study period and for 6 months after the completion of the study;
* Understand and sign the informed consent form.

Exclusion Criteria:

* Positive for human immunodeficiency virus (HIV) ;
* History of allergy to pemetrexed or bevacizumab;
* History of pemetrexed and/or bevacizumab intrathecal Injection;
* Presence of contraindication of bevacizumab:

  1. Uncontrolled hypertension(systolic pressure≥150mmHg，or diastolic pressure≥100mmHg；History of hypertensive crisis or hypertensive encephalopathy;
  2. Urine protein≥2+,or 24-hour urine protein≥2g；
  3. Unstable angina pectoris, symptomatic congestive heart failure,myocardial infarction within 6 months before enrollment, severe vascular disease, severe uncontrolled arrhythmia;
  4. Major hemoptysis within the past 1 month; History of coagulation disorders;
  5. Presence of serious non-healing wounds, ulcers, or bone fractures
  6. Presence of abdominal fistula, gastrointestinal perforation, or gastrointestinal tract obstruction;
  7. Presence of macrovascular invasion；
  8. Some neurological disorders unrelated to tumors，such as intracranial infection,cerebral hemorrhage,cerebral infarction,encephalitis;
* Brain/spinal cord radiation therapy within 1 week before enrollment;
* Pregnant and lactating female;
* Refuse to use contraception during the study period;
* Individuals considered by the investigator to be unsuitable for enrollment.